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TitleCryo-EM structures of hIAPP fibrils seeded by patient-extracted fibrils reveal new polymorphs and conserved fibril cores.
Journal, issue, pagesNat Struct Mol Biol, Vol. 28, Issue 9, Page 724-730, Year 2021
Publish dateSep 9, 2021
AuthorsQin Cao / David R Boyer / Michael R Sawaya / Romany Abskharon / Lorena Saelices / Binh A Nguyen / Jiahui Lu / Kevin A Murray / Fouad Kandeel / David S Eisenberg /
PubMed AbstractAmyloidosis of human islet amyloid polypeptide (hIAPP) is a pathological hallmark of type II diabetes (T2D), an epidemic afflicting nearly 10% of the world's population. To visualize disease-relevant ...Amyloidosis of human islet amyloid polypeptide (hIAPP) is a pathological hallmark of type II diabetes (T2D), an epidemic afflicting nearly 10% of the world's population. To visualize disease-relevant hIAPP fibrils, we extracted amyloid fibrils from islet cells of a T2D donor and amplified their quantity by seeding synthetic hIAPP. Cryo-EM studies revealed four fibril polymorphic atomic structures. Their resemblance to four unseeded hIAPP fibrils varies from nearly identical (TW3) to non-existent (TW2). The diverse repertoire of hIAPP polymorphs appears to arise from three distinct protofilament cores entwined in different combinations. The structural distinctiveness of TW1, TW2 and TW4 suggests they may be faithful replications of the pathogenic seeds. If so, the structures determined here provide the most direct view yet of hIAPP amyloid fibrils formed during T2D.
External linksNat Struct Mol Biol / PubMed:34518699
MethodsEM (helical sym.)
Resolution3.8 - 4.1 Å
Structure data

EMDB-23686, PDB-7m61:
Cryo-EM structure of human islet amyloid polypeptide (hIAPP, or amylin) fibrils seeded by patient extracted fibrils, polymorph 1
Method: EM (helical sym.) / Resolution: 3.8 Å

EMDB-23687, PDB-7m62:
Cryo-EM structure of human islet amyloid polypeptide (hIAPP, or amylin) fibrils seeded by patient extracted fibrils, polymorph 2
Method: EM (helical sym.) / Resolution: 3.9 Å

EMDB-23688, PDB-7m64:
Cryo-EM structure of human islet amyloid polypeptide (hIAPP, or amylin) fibrils seeded by patient extracted fibrils, polymorph 3
Method: EM (helical sym.) / Resolution: 4 Å

EMDB-23689, PDB-7m65:
Cryo-EM structure of human islet amyloid polypeptide (hIAPP, or amylin) fibrils seeded by patient extracted fibrils, polymorph 4
Method: EM (helical sym.) / Resolution: 4.1 Å

Source
  • homo sapiens (human)
KeywordsPROTEIN FIBRIL / hIAPP / type II diabetes / amyloid

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